Microdosing LSD fails to reduce symptoms in adult ADHD

In recent years, microdosing LSD has gained considerable attention as a potential treatment for psychiatric disorders. “Surveys and naturalistic studies have reported that individuals use microdosing LSD to self-treat various psychiatric disorders, including ADHD, with findings indicating a positive impact on symptoms,” wrote the researchers. “However, LSD’s efficacy in reducing ADHD symptoms remains unknown.” [JAMA Psychiatry 2025;doi:10.1001/jamapsychiatry.2025.0044]

Not better than placebo

“To our knowledge, this is the first double-blind, placebo-controlled RCT to investigate effects of repeated low-dose LSD administration in adults with ADHD,” noted the researchers.

Patients with moderate to severe ADHD (n=53; mean age, 37 years; female, 42 percent) were randomized to receive either LSD 20 μg or placebo twice weekly for 6 weeks. The primary outcome was change in ADHD symptoms from baseline to week 6, assessed by the Adult Investigator Symptom Rating Scale (AISRS). This was evaluated using a Mixed Model for Repeated Measures.

“The study did not meet its predefined primary endpoint [ie, change in ADHD symptoms from baseline to week 6 of treatment],” pointed out the researchers. There were improvements in mean AISRS in both the LSD and placebo groups, but the difference was not statistically or clinically significant (mean, -7.1 vs -8.9; difference, 1.8 points; 95 percent confidence interval [CI], -1.0 to ∞; p=0.80). Additionally, none of the primary sensitivity and secondary efficacy analyses reached significance.

A microdose of LSD is generally considered to be one-tenth to one-twentieth of a typical recreational dose. Microdoses or low doses of LSD typically range from 5 to 20 µg. “In our study, a rather high microdose [20 µg] was selected to increase the likelihood of detecting a positive response and efficacy. [Therefore,] it is unlikely that the dose was too low to be efficacious,” commented the researchers.

Placebo effect and high expectation

“Although the placebo effect was clear, it was not exceptionally pronounced in comparison with other studies in patients with ADHD,” said first author of the study, Dr Lorenz Müller of the Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland.

Interestingly, 80 percent of patients in the study guessed they had received LSD after the final dose. Those who believed they had received LSD demonstrated greater symptom improvement vs those who thought they had received placebo.

“Patients probably had excessively high expectations relating to the benefits of LSD, due to media reports. There is a hype surrounding the substance,” explained Liechti. “The supposed subjective treatment benefit is therefore due to the expectation of a benefit and the placebo effect rather than the actual substance.”

Safe in an outpatient setting

A total of 124 adverse events (AEs) occurred in the LSD group vs 64 in the placebo group. No serious AEs and no deaths were recorded. The most common treatment-related AEs were headache, nausea, insomnia, and visual alterations, but they were mostly mild, indicating that LSD was well-tolerated in an outpatient setting.